Effects of Lifestyle Changes on Semen Quality in Healthy Young Men Living in Highly Polluted Areas (FAST) (FAST)

January 7, 2020 updated by: LUIGI MONTANO, Azienda Sanitaria Locale Salerno

An Intervention Model for the Prevention of Infertility in Healthy Young Men Living in Highly Polluted Areas

We planned a randomized controlled trial (RCT) with the main aim to evaluate the effects of lifestyle changes on semen quality in healthy young men living in polluted areas in Italy. Secondary aims are to assess: a) the association between semen quality and biomarkers of early damage or inflammation; b) the associations between biomarkers of exposure to heavy metals and semen quality and biomarkers of early damage or inflammation; c) the associations between diet and physical activity and semen quality and biomarkers of early damage or inflammation; d) the effects of lifestyle changes on the blood and semen levels of heavy metals.

The RCT includes 450 young men living in one of the following three polluted areas:

  1. a polychlorinated biphenyls (PCBs) polluted area in Brescia province, Lombardy region;
  2. the valley of the Sacco river, with high levels of beta-hexachlorocyclohexane (β-HCH) originated by toxic waste dumps of industrial origin.
  3. the "Land of Fires" in the Campania region, with a high concentration of illegal waste dumping and uncontrolled burning near cultivated fields.

Inclusion criteria are: a) healthy males aged 18- 22 years; b) residents in the area since at least 5 years; c) non smokers; d) non alcohol or drug users; e) normo-weight (18.5< BMI<24.99); f) no occupationally exposed to fertility toxics; g) not affected by chronic diseases. Subjects will be randomly assigned to an intervention or control group. The intervention group will follow a nutritional pathway and receive suggestions on practice of physical activity for 4 months, under the guide of some nutritionists, who will establish individualized diets for each subject. The control group will receive only a booklet including the dietary recommendations by the Italian National Institute for Research on Food and Nutrition. All subjects will undergo urologic examination, measurement of weight, height and abdominal circumference, an interview on demographic data, lifestyle variables, dietary habits, adherence to Mediterranean diet and physical activity, and will provide blood and semen samples in fasting conditions, at the enrollment (baseline), at the end of the intervention phase (after 4 months) and at the end of follow-up (after 8 months).

Laboratory analyses include the following:

  • hematological parameters;
  • semen quality parameters;
  • prostate-specific antigen (PSA) in blood and semen;
  • RedOx status parameters in semen;
  • epigenetic analyses (DNA methylation) in blood lymphocytes and spermatozoa;
  • content of heavy metals in blood and semen. The project has been approved by the local Ethics Committees. Differences of means and proportions of all variables between the intervention and control group and the associations between diet, physical activity and sperm and blood parameters will be assessed using common statistical tests for comparisons of means and proportions as a first step.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Human semen quality is affected by genetic, metabolic, lifestyle and environmental factors. It is a sensitive marker of the general health status of an individual and a predictor of disease occurrence and mortality. Some studies suggested that a diet rich in anti-oxidant compounds and regular physical activity could improve semen quality. We planned a randomized controlled trial (RCT) with the main aim to evaluate the effects of lifestyle changes on semen quality in healthy young men living in three polluted areas in North, Centre and South Italy. Secondary aims are to assess: a) the association between semen quality and biomarkers of early damage or inflammation (prostate-specific antigen, RedOx status, epigenetic changes); b) the associations between biomarkers of exposure to toxic agents (heavy metals) and semen quality and biomarkers of early damage or inflammation; c) the associations between diet and physical activity and semen quality and biomarkers of early damage or inflammation; d) the effects of lifestyle changes on the blood and semen levels of heavy metals.

This RCT includes 450 healthy young men, aged 18-22 years, living in one of the following three polluted areas:

  1. a polychlorinated biphenyls (PCBs) polluted area in Brescia province, Lombardy region;
  2. the valley of the Sacco river, with high levels of beta-hexachlorocyclohexane (β-HCH) originated by toxic waste dumps of industrial origin.
  3. the "Land of Fires" in the Campania region, with a high concentration of illegal waste dumping and uncontrolled burning near cultivated fields.

According to a 1:1 randomization plan, the young men will be assigned to an intervention or control group.

The subjects will be enrolled among high school and university students, after a 20 minute meeting with students in each class, during a lesson, and in the presence of the teacher, for explaining the study design and inviting them to participate. After a short self-administered screening questionnaire for excluding subject not suitable to the research, the potential candidates are invited to undergo a urologic visit, in a Urology and Fertility Unit, including a clinical examination and spermiogram analysis. In the same time, participant undergo a fasting blood sample for the analysis of common parameters (glycemia, cholesterolemia, ecc.), and measures of height, weight and abdominal circumference by trained dieticians. Then each dietician evaluated each participant's dietary habits and physical activity using the European Prospective Investigation into Cancer (EPIC) and nutrition questionnaire, the PREvención con DIeta MEDiterránea (PREDIMED), and the International Physical Activity Questionnaire (IPAQ).

Each urological visit, blood and semen sampling will be repeated with the same methodology in both intervention and control groups, at time 0 (baseline, enrollment), after 4 months (end of the intervention) and after 8 months (end of follow-up).

The intervention for changing lifestyle in the experimental group has been planned on the basis of previous experience of educational intervention in nutritional epidemiology. It should be noted that the Mediterranean diet is the focus of the intervention and that the aim of the intervention is not to loss weight but to increase the amount of anti-oxidants and anti-inflammatory dietary compounds. It is well known that also motivated subjects have difficulties in changing dietary habits. Therefore the change will be based on the following points: personalized diet (according to taste and practical reasons), progressive change (one objective a time), frequent contacts with dieticians (weekly contacts in the first month). The subjects are also invited to share dieticians' indications with their parents and especially the person who usually cooks at home. The dietician intervention has been planned with the help of Dr. Stefania Ubaldi, President of the European Lifestyle Medicine Organization (ELMO), Geneva.

The subjects included in the control group will receive only a booklet with present recommendations for Mediterranean diet at the enrollment (baseline), and will further contact only after 4 and 8 months.

Blood and semen samples will be collected and stored at -80° according to a standard protocol up to the time of laboratory analysis. Laboratory analyses include the following:

  1. hematological parameters (whole blood count, glycemia, cholesterolemia, etc.);
  2. semen quality parameters, according to the 2010 World Health Organization (WHO) criteria;
  3. total and free prostate-specific antigen (PSA) in blood and semen;
  4. RedOx status parameters in semen;
  5. epigenetic analyses (DNA methylation) in blood lymphocytes and spermatozoa;
  6. ICP-MS (Inductively Coupled Plasma Mass Spectrometry) analyses of heavy metals - aluminum (Al), antimony (Sb), arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), calcium (Ca), chromium (Cr), cobalt (Co), cuprum (Cu), iron (Fe), lead (Pb), lithium (Li) magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), potassium (K), selenium (Se), sodium (Na), strontium (Sr) and zinc (Zn) in blood and semen.

Differences of means and proportions of all variables between the intervention and control group and the associations between diet, physical activity and sperm and blood parameters will be assessed using common statistical tests for comparisons of means and proportions as a first step. Multivariable models, including multi-factor analysis of variance, multiple regression and multiple logistic regression, will then be used for assessing the associations when taking account of possible confounders. All the statistical tests are two-sided with p=0.05 as the threshold for refusal of the null hypothesis.

The two Urology and Fertility Units: a) Unità Operativa Complessa di Urologia, Ospedale S. Francesco d'Assisi di Oliveto Citra (SA), Azienda Sanitaria Locale (ASL) Salerno and b) the Unit of Hygiene, epidemiology and biostatistics and Unit of Urology of the University of Brescia will provide routine hematological parameters (whole blood count, glycemia, cholesterolemia, etc.) and semen quality parameters, according to the 2010 WHO criteria.

Each recruitment unit will collect and treat the biological samples, which will be sent to the laboratories for the specific analysis:

  • Italian National Institute of Health, Rome: prostate-specific antigen in seminal plasma and in blood serum;
  • Institute of Food Sciences, Italian National Research Council (ISA-CNR) of Avellino: RedOx status parameters in semen and ICP-MS analyses of heavy metals
  • Epidemiology, Epigenetics And Toxicology (Epiget) Group of the University of Milan and Laboratory Biosafety and Risk Assessment of the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (SSPT-TECS-BIORISC CR ENEA Casaccia): epigenetic analyses (DNA methylation) in blood lymphocytes and spermatozoa, respectively.

The data management and statistical analysis will be performed by the Unit of Hygiene, epidemiology and biostatistics of the University of Brescia.

Study Type

Interventional

Enrollment (Actual)

363

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Brescia, Italy, 25123
        • Unit of Hygiene, Epidemiology and Public Health, University of Brescia
      • Brescia, Italy, 25128
        • Unit of Urology - Istituto Clinico Città di Brescia
      • Roma, Italy, 00161
        • Dpt. of Food safety, nutrition and veterinary public health, Italian National Institute of Health (ISS)
    • Salerno
      • Oliveto Citra, Salerno, Italy, 84020
        • Urology Unit "S. Francesco d'Assisi" Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 20 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Young healthy men aged 18-22 years, who have been living at least for 5 years in one of the recruitment areas (Lombardy Region, "Land of fires" or Valley of the Sacco river)
  • Normal weight (18,5 ≤ Body Mass Index < 25)
  • Waist circumference < 102cm
  • Having a normal sperm count (not azoospermic or cryptospermic)
  • Drinking less than 5 alcohol units a week (1AU=125ml)
  • Smoking less than 5 cigarettes (including e-cigarette, cigar, pipe)
  • Smoking marijuana less than 3 times a month
  • Must not have undergone urogenital surgery.
  • Must not have suffered cancer disease and/or undergone chemo/radiotherapy.

Exclusion Criteria:

  • Smoking more than 5 cigarettes a week
  • Smoking marijuana more than 3 times a month
  • Using drugs (other than marijuana)
  • Drinking more than 5 alcohol units a week (1AU=125ml)
  • Using dietary supplements (any type)
  • Having a prior urogenital surgery (for varicocele: up to 12 months before the enrollment)
  • Having suffered cancer and/or undergone chemo/radiotherapy
  • Using anti-inflammatory drug on a regular basis (such as cortisone and/or NSAIDs) and/or having taken one of those drugs up to 72 hours before the collection of blood and semen samples.
  • Using phosphodiesterase type 5 inhibitors (PDE5 inhibitor) up to 72 hours before the collection of blood and semen samples.
  • Using steroids and/or anabolic hormones.
  • Using dietary supplements and/or substances containing vegetal/animal extracts and/or trace elements up to 6 months before the enrollment.
  • Fever status and/or antibiotic therapy up to 2 weeks before the enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Subjects assigned to control group receives only a booklet including the recommendations for a correct diet by the Italian National Institute for Research on Food and Nutrition (INRAN), presently called (CRA-NUT) .
Experimental: Intervention

Subjects assigned to the intervention group will follow a nutritional pathway based on a Mediterranean diet pattern for 4 months and receive suggestions on the regular practice of physical activity, under the guide of some nutritionists, who will propose individualized diets for each subject.

All subjects of both groups will undergo urologic examination, measurement of weight, height and abdominal circumference, an interview on demographic data and lifestyle variables, and will provide blood and semen samples in fasting conditions, at the enrollment (baseline), at the end of the intervention phase (after 4 months) and at the end of follow-up (after 8 months).
Behavioral: lifestyle counseling
Nutritional plan and Physical activity goals

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes in spermatozoa motility
Time Frame: assessed at baseline, after 4 and 8 months
% total motility of spermatozoa
assessed at baseline, after 4 and 8 months
changes in Total Antioxidant Capacity (TAC)
Time Frame: assessed at baseline, after 4 and 8 months
Total Antioxidant Capacity, measured in semen samples (mM)
assessed at baseline, after 4 and 8 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sperm count
Time Frame: assessed at baseline, after 4 and 8 months from the enrollment
millions of spermatozoa/ml sample
assessed at baseline, after 4 and 8 months from the enrollment
PSA
Time Frame: assessed at baseline and after 4 months from the enrollment
Prostate-Specific Antigen in seminal plasma and in blood serum, measured in ng/ml
assessed at baseline and after 4 months from the enrollment
epigenetic analyses
Time Frame: assessed at baseline and after 4 months from the enrollment
DNA-methylation status of Alu and L1 sequences
assessed at baseline and after 4 months from the enrollment
Trace elements
Time Frame: assessed at baseline and after 4 months from the enrollment
dosage of trace elements in seminal plasma, semen and blood serum
assessed at baseline and after 4 months from the enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Sanitaria Locale Salerno

Collaborators

Istituto Superiore di Sanità
Università degli Studi di Brescia
Ministero della Salute, Italy
Istituto clinico Città di Brescia
ISA-CNR, Avellino
Molecular Epidemiology and Environmental Epigenetics Lab

Investigators

  • Principal Investigator: Luigi Montano, Dr, Urology Unit, "S. Francesco d'Assisi" Hospital, Oliveto Citra, A.S.L. Salerno

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2018

Primary Completion (Actual)

December 31, 2018

Study Completion (Actual)

November 6, 2019

Study Registration Dates

First Submitted

February 15, 2019

First Submitted That Met QC Criteria

July 8, 2019

First Posted (Actual)

July 9, 2019

Study Record Updates

Last Update Posted (Actual)

January 9, 2020

Last Update Submitted That Met QC Criteria

January 7, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • J59D1600132001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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